Carbachol, also known as carbamylcholine and sold under the brand name Miostat among others, is a

cholinomimetic A parasympathomimetic drug, sometimes called a cholinomimetic drug or cholinergic receptor stimulating agent, is a substance that stimulates the parasympathetic nervous system (PSNS). These chemicals are also called cholinergic drugs becaus ...

drug A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...

that binds and activates

acetylcholine receptors An acetylcholine receptor (abbreviated AChR) or a cholinergic receptor is an integral membrane protein that responds to the binding of acetylcholine, a neurotransmitter. Classification Like other transmembrane receptors, acetylcholine receptors ...

. Thus it is classified as a cholinergic agonist. It is primarily used for various ophthalmic purposes, such as for treating

glaucoma Glaucoma is a group of eye diseases that can lead to damage of the optic nerve. The optic nerve transmits visual information from the eye to the brain. Glaucoma may cause vision loss if left untreated. It has been called the "silent thief of ...

, or for use during ophthalmic surgery. It is generally administered as an ophthalmic solution (i.e.,

eye drop Eye drops or eyedrops are liquid drops applied directly to the surface of the eye usually in small amounts such as a single drop or a few drops. Eye drops usually contain saline to match the salinity of the eye. Drops containing only saline ...

s). Carbachol produces effects comparable to those of

sarin Sarin (NATO designation GB nerve_agent#G-series.html" ;"title="hort for nerve agent#G-series">G-series, "B" is an extremely toxic organophosphorus compound.extremely hazardous substance in the United States as defined in Section 302 of the U.S.

Emergency Planning and Community Right-to-Know Act The Emergency Planning and Community Right-to-Know Act of 1986 is a United States federal law passed by the 99th United States Congress located at Title 42, Chapter 116 of the U.S. Code, concerned with emergency response preparedness. On Octobe ...

(42 U.S.C. 11002), and is subject to strict reporting requirements by facilities which produce, store, or use it in significant quantities. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

Chemistry and pharmacology

Carbachol is a

choline Choline is a cation with the chemical formula . Choline forms various Salt (chemistry), salts, such as choline chloride and choline bitartrate. An essential nutrient for animals, it is a structural component of phospholipids and cell membrane ...

carbamate In organic chemistry, a carbamate is a category of organic compounds with the general Chemical formula, formula and Chemical structure, structure , which are formally Derivative (chemistry), derived from carbamic acid (). The term includes orga ...

and a positively charged quaternary ammonium compound. It is not well absorbed in the gastro-intestinal tract and does not cross the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...

. It is usually administered topical ocular or through intraocular injection. Carbachol is not easily metabolized by

cholinesterase The enzyme cholinesterase (EC 3.1.1.8, choline esterase; systematic name acylcholine acylhydrolase) catalyses the hydrolysis of choline-based esters: : an acylcholine + H2O = choline + a carboxylate Several of these serve as neurotransmitte ...

, it has a 2 to 5 minute onset of action and its duration of action is 4 to 8 hours with topical administration and 24 hours for intraocular administration. Since carbachol is poorly absorbed through topical administration,

benzalkonium chloride Benzalkonium chloride (BZK, BKC, BAK, BAC), also known as alkyldimethylbenzylammonium chloride (ADBAC) is a type of cationic surfactant. It is an organic salt classified as a quaternary ammonium compound. ADBACs have three main categories of use: ...

is mixed in to promote absorption. Carbachol is a

parasympathomimetic A parasympathomimetic drug, sometimes called a cholinomimetic drug or cholinergic receptor stimulating agent, is a substance that stimulates the parasympathetic nervous system (PSNS). These chemicals are also called cholinergic drugs becaus ...

that stimulates both

muscarinic A muscarinic acetylcholine receptor agonist, also simply known as a muscarinic agonist or as a muscarinic agent, is an agent that activates the activity of the muscarinic acetylcholine receptor. The muscarinic receptor has different subtypes, lab ...

and nicotinic receptors. In topical ocular and intraocular administration its principal effects are

miosis Miosis, or myosis (), is excessive constriction of the pupil.Farlex medical dictionary
citing: ...

and increased

aqueous humour The aqueous humour is a transparent water-like fluid similar to blood plasma, but containing low protein concentrations. It is secreted from the ciliary body, a structure supporting the lens of the eyeball. It fills both the anterior and the po ...

outflow. In the

cat The cat (''Felis catus''), also referred to as the domestic cat or house cat, is a small domesticated carnivorous mammal. It is the only domesticated species of the family Felidae. Advances in archaeology and genetics have shown that the ...

and

rat Rats are various medium-sized, long-tailed rodents. Species of rats are found throughout the order Rodentia, but stereotypical rats are found in the genus ''Rattus''. Other rat genera include '' Neotoma'' (pack rats), '' Bandicota'' (bandicoo ...

, carbachol is well known for its ability to induce rapid eye movement (REM) sleep when microinjected into the pontine reticular formation. Carbachol elicits this REM sleep-like state via activation of postsynaptic muscarinic

cholinergic Cholinergic agents are compounds which mimic the action of acetylcholine and/or butyrylcholine. In general, the word " choline" describes the various quaternary ammonium salts containing the ''N'',''N'',''N''-trimethylethanolammonium cation ...

receptors (

mAChRs Muscarinic acetylcholine receptors (mAChRs) are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-recepto ...

). A recent review indicates that carbachol is a strong promoter of ICC activity, which is mediated through the

calcium-activated chloride channel The Calcium-Dependent Chloride Channel (Ca-ClC) proteins (or calcium-activated chloride channels (CaCCs), are heterogeneous groups of ligand-gated ion channels for chloride that have been identified in many epithelial and endothelial cell types a ...

, anoctamin 1.

Synthesis

Carbachol may be prepared in a 2 step process beginning with the reaction of

2-chloroethanol 2-Chloroethanol (also called ethylene chlorohydrin or glycol chlorohydrin) is an organic chemical compound with the chemical formula HOCH2CH2Cl and the ''simplest'' beta-halohydrin (chlorohydrin). This colorless liquid has a pleasant ether-like od ...

with

urea Urea, also called carbamide (because it is a diamide of carbonic acid), is an organic compound with chemical formula . This amide has two Amine, amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest am ...

to form a 2-chloroethyl-

, which is then quaternised by a reaction with

trimethylamine Trimethylamine (TMA) is an organic compound with the formula N(CH3)3. It is a trimethylated derivative of ammonia. TMA is widely used in industry. At higher concentrations it has an ammonia-like odor, and can cause necrosis of mucous membranes ...

Indications

Carbachol is primarily used in the treatment of

, but it is also used during ophthalmic surgery. Carbachol eyedrops are used to decrease the pressure in the eye for people with glaucoma. It is sometimes used to constrict the pupils during

cataract A cataract is a cloudy area in the lens (anatomy), lens of the eye that leads to a visual impairment, decrease in vision of the eye. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colours, blurry or ...

surgery. Topical ocular administration is used to decrease intraocular pressure in people with primary open-angle

. Intraocular administration is used to produce miosis after lens implantation during cataract surgery. Carbachol can also be used to stimulate bladder emptying to treat the condition of underactive bladder. In most countries carbachol is only available by prescription. Outside the United States, it is also indicated for urinary retention as an oral (2 mg) tablet.

Contraindications

Use of carbachol, as well as all other muscarinic receptor agonists, is contraindicated in patients with

asthma Asthma is a common long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wh ...

, coronary insufficiency, gastroduodenal

ulcers An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing ...

, and

incontinence Incontinence or Incontinent may refer to: * Urinary incontinence, the most commonly occurring type of incontinence, the involuntary excretion of urine *Fecal incontinence Fecal incontinence (FI), or in some forms, encopresis, is a lack of con ...

. The

action of this drug will exacerbate the

symptoms Signs and symptoms are diagnostic indications of an illness, injury, or condition. Signs are objective and externally observable; symptoms are a person's reported subjective experiences. A sign for example may be a higher or lower temperature ...

of these disorders.

Overdose

The effects of a systemic overdose will probably be similar to the effects of a

nerve agent Nerve agents, sometimes also called nerve gases, are a class of organic chemistry, organic chemicals that disrupt the mechanisms by which nerves transfer messages to organs. The disruption is caused by the blocking of acetylcholinesterase (ACh ...

(they both act on the cholinergic system, increasing cholinergic transmission), but its toxicity is much weaker and it is easier to antagonize in overdose. When administered ocularly there is little risk of such effects, since the doses are much smaller (see topical versus systemic administration).

References

External links

* {{Portal bar , Medicine Carbamates Choline esters M1 receptor agonists M2 receptor agonists M3 receptor agonists M4 receptor agonists M5 receptor agonists Nicotinic agonists Ophthalmology drugs Peripherally selective drugs Quaternary ammonium compounds